The invention provides novel compounds that have demonstrated biological activity. The compounds also demonstrate surprising and significant improvement in physical properties, such as solubility and stability.
The compounds of the invention are based on leptin sequences disclosed in U.S. Application No. 61/387,402 and U.S. Application No. 61/422,091. The compounds are surprisingly highly soluble and do not demonstrate the propensity to aggregate, unlike the naturally occurring leptins. The physical properties of the compounds facilitate the preparation of soluble, pharmaceutically acceptable formulations and compositions, also provided by the invention. Diseases amenable to such treatment include lipodystrophy, dyslipidemia, hyperlipidemia, overweight, obesity, hypothalamic amenorrhea, Alzheimer's disease, leptin deficiency, fatty liver disease, diabetes (including type I and type II), nonalcoholic steatohepatitis (NASH), nonalcoholic fatty liver disease (NAFLD), metabolic syndrome X, and Huntington's Disease, or combinations thereof.
There remains a need to develop polypeptides useful in the above described metabolic diseases, conditions and disorders. Accordingly, it is an object of the present invention to provide novel polypeptides useful to treat the above conditions and methods for producing and using them.
Each patent, patent application, and publication cited herein is hereby incorporated herein by reference in its entirety and for all purposes.